Lactobacillus Reuteri

• Gut microbiome balance
• Immune system modulation
• Oral health support
• Pathogen inhibition

• Vitamin B12 production
• Reduction of infantile colic
• Cholesterol management
• Anti-inflammatory effects
• Potential bone health support
• Stress and anxiety reduction
• Potential metabolic health benefits
• Oral cavity health improvement

Lactobacillus reuteri exerts its beneficial effects through multiple mechanisms that contribute to gut health, immune modulation, and protection against pathogens. One of its most distinctive features is the production of reuterin (3-hydroxypropionaldehyde), a broad-spectrum antimicrobial compound that inhibits the growth of various pathogenic bacteria, fungi, and protozoa. Reuterin works by disrupting the function of ribonucleotide reductase, an enzyme essential for DNA synthesis in many microorganisms. This antimicrobial activity helps L.

reuteri to compete effectively against pathogens in the gut environment and contributes to maintaining a balanced microbiota. L. reuteri also produces other antimicrobial compounds, including organic acids (primarily lactic acid), hydrogen peroxide, and bacteriocins, which further enhance its ability to inhibit pathogenic microorganisms. The production of lactic acid creates an acidic environment in the gut that is unfavorable for many pathogenic bacteria while promoting the growth of beneficial bacteria.

In terms of gut barrier function, L. reuteri strengthens the intestinal epithelial barrier by enhancing tight junction proteins between epithelial cells, thereby reducing intestinal permeability and preventing the translocation of pathogens and toxins across the intestinal wall. This ‘leaky gut’ prevention is crucial for reducing systemic inflammation and endotoxemia. L.

reuteri has significant immunomodulatory effects, interacting with the gut-associated lymphoid tissue (GALT) to influence both innate and adaptive immunity. It enhances the activity of natural killer cells, macrophages, and dendritic cells, which are crucial components of the innate immune system. L. reuteri also promotes the production of secretory IgA antibodies, which provide mucosal protection against pathogens.

A particularly important aspect of L. reuteri’s immune modulation is its ability to induce regulatory T cells (Tregs) and increase the production of anti-inflammatory cytokines like IL-10, while reducing pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. This helps to maintain immune homeostasis and prevent excessive inflammation in the gut. Certain strains of L.

reuteri, particularly NCIMB 30242, have demonstrated the ability to reduce cholesterol levels through multiple mechanisms, including bile salt hydrolase activity. This enzyme deconjugates bile acids, leading to their excretion and forcing the body to use cholesterol to synthesize new bile acids, thereby reducing serum cholesterol levels. L. reuteri is one of the few probiotic species capable of producing vitamin B12 (cobalamin), an essential nutrient involved in DNA synthesis, red blood cell formation, and neurological function.

This production may contribute to its health benefits, particularly in individuals with limited dietary intake of B12. In the oral cavity, L. reuteri inhibits the growth of pathogenic bacteria associated with dental caries, periodontal disease, and halitosis. It competes with these pathogens for adhesion sites on oral surfaces and produces antimicrobial compounds that directly inhibit their growth.

L. reuteri also modulates the gut-brain axis through multiple pathways, including the production of neurotransmitters and neuroactive compounds, the modulation of the vagus nerve signaling, and the reduction of systemic inflammation. This may explain its observed effects on stress, anxiety, and mood in some studies. In infants, L.

reuteri has been shown to reduce the symptoms of colic, potentially through multiple mechanisms including modulation of gut motility, reduction of inflammation, and inhibition of gas-producing bacteria. Strain-specific effects are particularly important for L. reuteri. Different strains have been shown to have distinct effects and mechanisms of action.

For example, L. reuteri DSM 17938 has shown particular efficacy for infantile colic, while L. reuteri NCIMB 30242 has demonstrated cholesterol-lowering effects. The strain L.

reuteri ATCC PTA 6475 has shown strong anti-inflammatory properties and potential benefits for bone health through the inhibition of TNF-induced bone loss.

The optimal dosage of Lactobacillus reuteri varies depending on the specific condition being addressed, the strain used, and individual factors. Generally, dosages range from 100 million to 10 billion colony-forming units (CFU) per day for general health maintenance, while therapeutic dosages for specific conditions may range from 1 billion to 20 billion CFU daily. It’s important to note that efficacy is not solely determined by CFU count but also by strain specificity, viability at the site of action, and the particular health condition being addressed. Different strains of L.

reuteri (such as DSM 17938, NCIMB 30242, ATCC PTA 6475) have been studied at different dosages for various conditions.

Lactobacillus reuteri is not ‘absorbed’ in the traditional sense of dietary supplements. Instead, its bioavailability refers to the percentage of live bacteria that survive the harsh conditions of the gastrointestinal tract to reach their site of action. L. reuteri has relatively good acid and bile resistance compared to many other probiotic species, which contributes to its survival through the stomach and upper intestine.

Studies suggest that approximately 20-40% of orally administered L. reuteri may survive passage through the stomach and upper intestine, though this varies widely depending on formulation, strain characteristics, and individual factors such as gastric acidity and transit time. Once it reaches the intestines, L. reuteri can temporarily colonize the gut mucosa, with detectable levels persisting for 1-2 weeks after discontinuation in many individuals.

L. reuteri has demonstrated good adhesion to intestinal epithelial cells and mucus, which enhances its residence time and functional effects in the gut. This adhesion ability varies between strains, with some strains showing particularly strong adhesion properties. For oral health applications, L.

reuteri can also colonize the oral cavity temporarily, adhering to oral surfaces and providing localized benefits. When administered to infants, L. reuteri has shown good colonization of the developing gut microbiome, with some studies suggesting it may persist longer in infants than in adults due to the less competitive microbial environment.

Enteric coating: Protects probiotics from stomach acid, increasing survival rates by 30-60%, Microencapsulation: Shields bacteria from environmental stressors, potentially improving viability by 40-70%, Delayed-release capsules: Designed to release probiotics in the intestines rather than the stomach, Buffered formulations: Include compounds that neutralize stomach acid around the bacteria, Prebiotic inclusion (synbiotics): Provides nutrients that support probiotic growth and colonization, particularly fructooligosaccharides (FOS) and inulin, Higher CFU counts: Compensates for die-off during transit, though quality and strain characteristics are more important than quantity alone, Refrigerated storage: Maintains viability before consumption, Consumption with meals: Food can buffer stomach acid and improve survival, Oil-based delivery systems: Particularly for infant drops, oil can provide protection from gastric conditions, Freeze-dried preparations: Maintain stability until hydration in the digestive tract, Selection of acid-resistant strains: Some strains of L. reuteri have naturally higher acid resistance than others

For maximum effectiveness, L. reuteri supplements are best taken with or just before meals, which helps buffer stomach acid and improve survival rates. When taken for general digestive health, consistent daily supplementation is more important than specific timing. Morning administration may be preferable for some individuals as gastric emptying tends to be faster in the morning, potentially allowing more bacteria to reach the intestines.

For cholesterol management (particularly with the NCIMB 30242 strain), taking L. reuteri with a meal containing fat may enhance its bile salt hydrolase activity and cholesterol-lowering effects. For oral health applications, L. reuteri lozenges or chewable tablets are best used after brushing teeth, allowing direct contact with oral tissues before swallowing.

For infants with colic, L. reuteri drops (typically the DSM 17938 strain) are usually administered 30 minutes before feeding to allow the probiotic to reach the intestines ahead of food. When used as an adjunct to H. pylori treatment, L.

reuteri should be taken at a different time than the antibiotic regimen, ideally with food. When taken for immune support, consistent daily use is more important than timing, though some practitioners recommend morning administration to align with natural circadian rhythms of immune function. For maximum colonization potential, consistent daily use at approximately the same time each day is recommended, as L. reuteri typically remains in the gut for only 1-2 weeks after discontinuation.

For bone health applications (particularly with the ATCC PTA 6475 strain), taking L. reuteri with calcium-containing foods may theoretically enhance its potential benefits for bone metabolism, though this has not been specifically studied.

• Temporary digestive discomfort (gas, bloating)
• Mild abdominal cramping
• Increased thirst (rare)
• Headache (rare)
• Constipation (rare)
• Increased appetite (rare)
• Nausea (rare)
• Taste disturbances (rare, primarily with oral lozenges)

• Severely immunocompromised patients (e.g., those with AIDS, lymphoma, or undergoing long-term corticosteroid treatment)
• Patients with short bowel syndrome
• Individuals with central venous catheters
• Critically ill patients in intensive care units
• Premature infants (especially very low birth weight infants)
• Patients with damaged heart valves or artificial heart valves
• Known hypersensitivity to Lactobacillus species or any components of the probiotic formulation

• Antibiotics (may reduce probiotic effectiveness; separate administration by at least 2 hours)
• Immunosuppressants (theoretical increased risk of infection)
• Antifungal medications (may reduce probiotic effectiveness)
• Medications that decrease stomach acid (may increase probiotic survival but potentially affect colonization patterns)
• Anticoagulants/antiplatelet drugs (rare case reports of increased bleeding risk with certain probiotics, though not specifically with L. reuteri)

No established upper limit for L. reuteri. Doses up to 20 billion CFU daily have been used in clinical studies without significant adverse effects in healthy individuals. However, higher doses may increase the risk of side effects such as digestive discomfort without necessarily providing additional benefits.

The appropriate dose depends on the specific condition being treated, the strain being used, and individual factors. For general health maintenance, 1-10 billion CFU daily is typically sufficient. For infants with colic, the extensively studied dose is 100 million CFU daily of the DSM 17938 strain, with no benefit observed at higher doses. Individuals with compromised immune systems should consult healthcare providers before using any dose of probiotics.

It’s important to note that safety concerns are more related to an individual’s health status than to specific dosage thresholds.

Lactobacillus reuteri has an excellent safety profile and has been consumed in traditional fermented foods for centuries. It has Generally Recognized as Safe (GRAS) status in the United States and Qualified Presumption of Safety (QPS) status in the European Union. L. reuteri is one of the few probiotic species that has been extensively studied in infants, including those with colic, with an excellent safety record.

The DSM 17938 strain in particular has been used in numerous clinical trials in infants without significant adverse effects. There have been extremely rare cases of Lactobacillus bacteremia (bacteria in the blood) in severely immunocompromised individuals or those with serious underlying health conditions, though L. reuteri is less commonly implicated than some other Lactobacillus species. While L.

reuteri has a long history of safe use in foods and supplements, caution is advised in certain populations. Individuals with severe acute pancreatitis should avoid probiotics, as some studies have suggested potential harm in this specific condition. Those with a history of endocarditis or artificial heart valves should consult healthcare providers before use. Diabetic patients should check probiotic supplement labels for added sugars.

Individuals with milk allergies should ensure that dairy-free formulations are selected, as some L. reuteri products are cultured in dairy-based media. Patients scheduled for surgery should inform their healthcare providers about probiotic use, as some practitioners recommend discontinuation 1-2 weeks before major surgical procedures. While L.

reuteri has been consumed during pregnancy in traditional foods for centuries and is generally considered safe, pregnant women should still consult healthcare providers before starting any supplement regimen. Long-term safety studies on L. reuteri, particularly the DSM 17938 strain, have shown no adverse effects with continuous use over many years, making it suitable for ongoing supplementation in healthy individuals.

Lactobacillus reuteri has achieved favorable regulatory status in most major markets worldwide, reflecting its long history of safe use and substantial scientific evidence supporting its benefits. In the United States, L. reuteri has Generally Recognized as Safe (GRAS) status, allowing its use in foods and dietary supplements. Several specific strains, including DSM 17938 and NCIMB 30242, have received self-affirmed GRAS status for particular applications.

In the European Union, L. reuteri has Qualified Presumption of Safety (QPS) status granted by the European Food Safety Authority (EFSA), permitting its use in food and supplements. However, the EU has stricter regulations regarding probiotic health claims, and most L. reuteri products cannot make specific health claims on their labels without additional approval.

In Canada, L. reuteri is approved for use in Natural Health Products (NHPs) and has received specific strain-level approvals for certain health claims, particularly for the DSM 17938 strain for infantile colic and the NCIMB 30242 strain for cholesterol management. Japan has approved L. reuteri as a Food for Specified Health Use (FOSHU) ingredient, allowing certain health claims based on scientific evidence.

Australia and New Zealand regulate L. reuteri through the Food Standards Australia New Zealand (FSANZ) and the Therapeutic Goods Administration (TGA), with various strains approved for use in foods and complementary medicines. In China, L. reuteri is approved for use in foods and health supplements, with regulations continuing to evolve as the probiotic market expands.

Many other countries worldwide permit the use of L. reuteri in foods and supplements, though specific regulations vary regarding permitted health claims, labeling requirements, and quality standards. The regulatory status of L. reuteri is generally more favorable than many other probiotic species due to its extensive safety record, particularly in infant applications, and the substantial body of clinical research supporting its benefits.

When developing or marketing Lactobacillus reuteri products, several important regulatory considerations should be taken into account. Strain specificity is crucial, as regulatory approvals and scientific evidence are often specific to particular strains of L. reuteri (e.g., DSM 17938, NCIMB 30242, ATCC PTA 6475). Using the exact strain mentioned in clinical studies is essential for making related claims.

Health claim limitations vary significantly by region, with the EU having particularly strict requirements for probiotic health claims. In many regions, structure/function claims are permitted while disease prevention or treatment claims are prohibited without drug approval. Quality control documentation is essential, including certificates of analysis, stability data, and manufacturing process validation. Many regions require specific labeling elements, including the full taxonomic name (Lactobacillus reuteri or Limosilactobacillus reuteri), the specific strain designation when relevant, CFU count, and appropriate storage conditions.

For infant products, additional safety documentation and quality controls are typically required, though L. reuteri DSM 17938 has an extensive safety record in this population. Post-market surveillance systems should be established to monitor and report any adverse events, which is particularly important for maintaining regulatory compliance in many regions. When combining L.

reuteri with other ingredients, additional regulatory considerations may apply to the combination product. For products targeting specific health conditions like cholesterol management or infantile colic, the level of supporting evidence required varies by regulatory jurisdiction. Some regions have specific regulations regarding the viability of probiotics throughout shelf life, requiring guarantee of the stated CFU count until the expiration date, not just at the time of manufacture. For novel applications or delivery systems, additional safety and efficacy data may be required by regulatory authorities.

When exporting L. reuteri products internationally, it’s essential to comply with the specific regulations of each target market, which may require reformulation or relabeling. The regulatory landscape for probiotics continues to evolve, necessitating ongoing monitoring of regulatory developments and updates to compliance strategies as needed.

The cost of Lactobacillus reuteri supplements varies significantly based on strain specificity, formulation, brand reputation, and intended application. Specialized infant drops containing L. reuteri DSM 17938 typically range from $25-45 for a 30-day supply, making them among the more expensive probiotic formulations on a per-day basis ($0.83-1.50 per day). However, these specialized products have the most robust clinical evidence for infantile colic.

General L. reuteri supplements in capsule or tablet form for adults typically range from $20-40 for a 30-day supply ($0.67-1.33 per day), positioning them in the mid-to-high range of probiotic supplements. Strain-specific formulations for targeted applications (such as NCIMB 30242 for cholesterol management or specific strains for oral health) often command premium prices, ranging from $30-60 for a 30-day supply ($1.00-2.00 per day). Multi-strain probiotics that include L.

reuteri among other probiotic species typically range from $25-50 for a 30-day supply ($0.83-1.67 per day), offering potential synergistic benefits but often containing lower amounts of each individual strain. Compared to other probiotic species, L. reuteri supplements tend to be moderately more expensive than common probiotics like L. acidophilus or Bifidobacterium species, reflecting their more specialized applications and extensive research.

When compared to pharmaceutical interventions for similar conditions, L. reuteri supplements are generally more cost-effective. For example, L. reuteri DSM 17938 for infantile colic ($25-45/month) is less expensive than many prescription medications for colic symptoms, with fewer side effects.

Similarly, L. reuteri NCIMB 30242 for cholesterol management ($30-60/month) is significantly less expensive than many prescription cholesterol medications, though it may have more modest effects. For oral health applications, L. reuteri lozenges or chewable tablets ($25-40/month) are comparable in cost to specialized oral care products but offer a different mechanism of action that may complement traditional oral hygiene practices.

When evaluating the cost-effectiveness of Lactobacillus reuteri supplements, several value considerations should be taken into account. Strain specificity is crucial for targeted benefits, with certain strains having stronger evidence for specific applications. For infantile colic, the DSM 17938 strain has the most robust evidence, making strain-specific products potentially more valuable despite higher costs. For cholesterol management, the NCIMB 30242 strain has demonstrated efficacy, while the ATCC PTA 6475 strain shows promise for bone health.

The guaranteed CFU count through expiration (not just at manufacture) is an important quality indicator that may justify higher prices. Some premium products guarantee 100% of the stated potency at expiration, while lower-cost alternatives may contain significantly fewer viable bacteria by the time they’re consumed. Delivery system technology, such as enteric coating, microencapsulation, or specialized formulations for targeted release, can enhance probiotic survival and efficacy, potentially justifying higher costs. For infant products, oil-based suspensions that protect the bacteria and facilitate easy administration may offer better value despite higher prices.

Third-party testing and quality certifications (such as USP Verified, NSF Certified, or specific testing for potency and purity) can provide assurance of product quality and may warrant premium pricing. For specific health concerns, the potential cost savings from avoiding more expensive interventions should be considered. For example, effective management of infantile colic with L. reuteri may reduce healthcare visits and parental work absenteeism, providing economic benefits beyond the supplement cost.

Similarly, cholesterol management with L. reuteri may complement other interventions and potentially reduce long-term healthcare costs. The research support for specific products varies widely, with some brands investing in clinical studies on their specific formulations, potentially justifying higher prices for these evidence-backed products. For general health maintenance, less expensive L.

reuteri supplements may provide adequate benefits, while specific health concerns may warrant investment in premium, strain-specific, clinically-studied products. The cost per billion CFU varies widely across products, making it important to calculate this metric when comparing options. Some seemingly expensive products may actually offer better value when the potency is considered. Stability and shelf life should also factor into value considerations, as products with longer shelf life and better stability may reduce waste from expired supplements.

To optimize the cost-effectiveness of Lactobacillus reuteri supplementation, consider several practical strategies. For general digestive health, multi-strain probiotics that include L. reuteri among other beneficial strains may offer better value than single-strain products, providing broader benefits at a similar price point. However, for specific conditions like infantile colic or cholesterol management, investing in strain-specific formulations (DSM 17938 or NCIMB 30242, respectively) may be more cost-effective despite higher upfront costs.

Subscription services offered by many supplement companies can reduce costs by 10-15% while ensuring consistent supply. Bulk purchasing (2-6 month supply) often provides significant discounts, though this should be balanced against shelf life considerations. Some healthcare practitioners and nutritionists can provide professional-grade supplements at discounted prices, which may offer better quality-to-price ratios than retail options. For those with Health Savings Accounts (HSAs) or Flexible Spending Accounts (FSAs), many L.

reuteri supplements qualify as eligible expenses with appropriate documentation, effectively reducing costs through tax savings. Proper storage according to manufacturer instructions (refrigeration when recommended) maximizes viability and ensures you’re getting the full value from each dose. For families, infant-specific formulations can sometimes be adapted for adult use by adjusting the dosage, potentially reducing the need for multiple products, though this should be discussed with a healthcare provider. Some insurance plans cover probiotics with a prescription, particularly for specific medical conditions, potentially reducing out-of-pocket costs.

Comparing cost per billion CFU rather than just the sticker price provides a more accurate value assessment across different products and brands. For those primarily interested in L. reuteri for general health, incorporating naturally fermented foods containing lactic acid bacteria into the diet may provide some benefits at a lower cost than supplements, though the specific strains and amounts will vary. Timing purchases around sales events or using coupon codes can reduce costs by 10-25% at many retailers.

For ongoing supplementation, rotating between higher-cost, premium formulations and more affordable options may balance cost and benefits, particularly for general health maintenance rather than specific therapeutic uses.

The shelf life of Lactobacillus reuteri products varies significantly based on formulation, packaging, and storage conditions. Properly manufactured and stored freeze-dried L. reuteri supplements typically maintain acceptable viability for 18-24 months from the date of manufacture. L.

reuteri has demonstrated relatively good stability compared to many other probiotic species, with some properly formulated products maintaining viability for up to 24-36 months at room temperature. This enhanced stability is partly due to L. reuteri’s natural resistance to environmental stressors. Oil-based L.

reuteri drops for infants (particularly the DSM 17938 strain) typically have a shelf life of 18-24 months when stored according to label instructions, with the oil matrix providing additional protection from environmental stressors. Refrigerated liquid formulations generally have a shorter shelf life of 2-3 months. Microencapsulated or specially formulated shelf-stable products may maintain viability for up to 24-36 months at room temperature. L.

reuteri lozenges or chewable tablets for oral health applications typically have a shelf life of 18-24 months when stored in a cool, dry place.

Refrigeration (36-46°F/2-8°C) is optimal for most L. reuteri supplements, even those labeled as shelf-stable, as it significantly extends viability. If refrigeration is not possible, store in a cool, dry place away from direct sunlight, heat sources, and humidity. Temperature fluctuations should be minimized, as repeated warming and cooling can reduce viability.

Keep containers tightly closed when not in use to prevent moisture exposure. For blister-packed probiotics, only remove capsules/tablets when ready to consume. Liquid formulations almost always require refrigeration after opening. Oil-based infant drops containing L.

reuteri DSM 17938 typically require refrigeration after opening, though some formulations may be stable at room temperature for a limited time (check product-specific instructions). Follow manufacturer-specific storage instructions, as some advanced formulations may have different requirements. When traveling, consider using insulated containers with ice packs for temperature-sensitive formulations, or look for specially designed shelf-stable travel formulations. L.

reuteri has demonstrated relatively good stability at room temperature compared to many other probiotic strains, but refrigeration will still extend its shelf life. For lozenges or chewable tablets for oral health, store in a cool, dry place and keep the container tightly closed to prevent moisture exposure, which can activate the probiotics prematurely.

Heat: Temperatures above 77°F/25°C accelerate die-off of live bacteria; exposure to temperatures above 104°F/40°C can cause rapid loss of viability. L. reuteri has somewhat better heat resistance than some other probiotic species but is still sensitive to high temperatures., Moisture: Exposure to humidity or moisture activates freeze-dried bacteria prematurely, depleting their energy reserves and reducing shelf life., Oxygen: L. reuteri is microaerophilic (prefers low oxygen), and excessive oxygen exposure can reduce viability through oxidative damage, though it is more oxygen-tolerant than some strictly anaerobic probiotics., Light: Direct sunlight and UV light can damage bacterial cells through photodegradation and generation of reactive oxygen species., pH extremes: While L. reuteri is relatively acid-tolerant compared to many probiotics, extreme pH conditions during storage can still reduce viability., Freeze-thaw cycles: Repeated freezing and thawing creates ice crystals that can damage bacterial cell walls., Chemical preservatives: Many preservatives used in foods and supplements are designed to inhibit microbial growth and may affect probiotic viability., Compression and processing: Mechanical stress during manufacturing and compression into tablets can damage bacterial cells., Interaction with other ingredients: Certain active ingredients in multi-component supplements may have antimicrobial properties that reduce probiotic viability over time.

Several technologies have been developed to enhance the stability of L. reuteri products. Microencapsulation protects bacteria with a protective coating that shields them from environmental stressors and controls their release. Freeze-drying (lyophilization) removes water while preserving the cellular structure, significantly extending shelf life.

Addition of cryoprotectants like trehalose, sucrose, or glycerol helps protect bacterial cells during freeze-drying and storage. Oil-based suspension, particularly for infant drops containing L. reuteri DSM 17938, provides protection from oxygen, moisture, and pH fluctuations, enhancing stability. Specialized packaging such as nitrogen-flushed bottles, blister packs, or aluminum foil sachets reduces exposure to oxygen and moisture.

Some formulations include prebiotics that not only support growth in the gut but may also enhance stability during storage. Advanced formulations may incorporate acid-resistant strains (L. reuteri is naturally relatively acid-resistant) or add buffering agents to protect against pH fluctuations. Vacuum-sealed packaging removes oxygen that could damage sensitive probiotic strains.

Cold-chain management throughout manufacturing, distribution, and retail ensures optimal temperature conditions are maintained. Some manufacturers use overages (adding more CFUs than stated on the label) to compensate for expected die-off during shelf life, ensuring that the product contains at least the labeled amount of viable probiotics through the expiration date. Recent innovations include the use of novel delivery systems such as microgels, biopolymer matrices, and lipid-based encapsulation to enhance the stability and targeted delivery of L. reuteri.

Synthesis Methods

Natural Sources

Quality Considerations

Lactobacillus reuteri has been consumed by humans throughout history, primarily through naturally fermented foods and mother’s milk, though it wasn’t identified as a distinct species until the 20th century. Traditional fermented foods from various cultures likely contained L. reuteri among other lactic acid bacteria, contributing to their preservation and potential health benefits. These include traditional fermented dairy products like kefir, some types of yogurt, and certain artisanal cheeses, particularly those made using traditional methods without pasteurization.

Some traditional sourdough breads, especially those made with extended fermentation periods and traditional starters, may have contained L. reuteri. Various fermented vegetables from different cultural traditions, such as some varieties of sauerkraut, kimchi, and pickled vegetables, may have harbored L. reuteri, though in variable amounts.

Certain traditional fermented meat products, particularly those made using natural fermentation processes, might have contained L. reuteri as part of their microbial community. Throughout human history, the primary natural source of L. reuteri for infants has been breast milk and maternal microbiota transferred during birth and early life.

This natural inoculation with L. reuteri and other beneficial bacteria was an important aspect of infant health before the modern era. While not explicitly recognized as L. reuteri, the benefits of these fermented foods were acknowledged in many traditional medical systems.

For example, fermented dairy products were recommended for digestive health in various traditional healing practices across cultures. The consumption of fermented foods during pregnancy and lactation, as well as their introduction to children, was common in many traditional cultures, potentially providing a natural source of L. reuteri and other beneficial bacteria.

The modern scientific history of Lactobacillus reuteri began in the 1960s when it was first isolated from human intestinal samples by German microbiologist Gerhard Reuter, after whom the species was named. Initially classified as Lactobacillus fermentum biotype II, it was later recognized as a distinct species and officially named Lactobacillus reuteri in 1980 by Kandler and colleagues. In the 1980s and 1990s, researchers began to investigate the unique properties of L. reuteri, including its ability to produce reuterin, a broad-spectrum antimicrobial compound.

This discovery highlighted L. reuteri’s potential as a probiotic with distinctive mechanisms for inhibiting pathogens. The first commercial probiotic products containing L. reuteri were developed in the late 1990s, initially focusing on general digestive health applications.

The early 2000s saw the beginning of strain-specific research, with particular attention to strains like ATCC 55730 (later replaced by DSM 17938 due to transferable antibiotic resistance genes in the original strain), NCIMB 30242, and ATCC PTA 6475. Each of these strains has been studied for specific health applications. A significant breakthrough came in the mid-2000s when clinical trials demonstrated the effectiveness of L. reuteri DSM 17938 for infantile colic, establishing this strain as a leading probiotic for pediatric applications.

Around the same time, research on L. reuteri NCIMB 30242 revealed its cholesterol-lowering properties, opening up applications in cardiovascular health. In the 2010s, research expanded to explore L. reuteri’s potential benefits for oral health, bone density, immune function, and metabolic health.

The strain ATCC PTA 6475 showed particular promise for bone health in preclinical studies. Recent taxonomic revisions have proposed reclassifying L. reuteri into a new genus, Limosilactobacillus, though both names remain in use in scientific and commercial contexts. Today, L.

reuteri is one of the most well-studied probiotic species, with strain-specific applications supported by numerous clinical trials. It is commercially available in various formulations, including infant drops, capsules, tablets, lozenges, and as an ingredient in certain fermented dairy products.

Recent developments in Lactobacillus reuteri research and applications have expanded our understanding of this probiotic’s potential benefits and mechanisms of action. Advanced genomic and metagenomic analyses have provided deeper insights into the strain-specific properties of L. reuteri and its interactions with the host microbiome. This has led to more targeted applications based on specific genetic capabilities of different strains.

Research into the gut-brain axis has revealed potential neurological benefits of L. reuteri, with animal studies showing effects on social behavior, stress response, and anxiety through vagus nerve signaling and neurotransmitter modulation. Some preliminary human studies are now exploring these effects. The role of L.

reuteri in bone health has been further elucidated, with the ATCC PTA 6475 strain showing promise for preventing bone loss through anti-inflammatory mechanisms. Human clinical trials in this area are ongoing. New delivery systems have been developed to enhance L. reuteri’s stability and efficacy, including advanced microencapsulation techniques, synbiotic formulations, and targeted-release technologies.

The use of L. reuteri in combination with other probiotics in multi-strain formulations has been increasingly studied, with evidence suggesting synergistic effects for certain health applications. Research into L. reuteri’s immunomodulatory properties has expanded, with studies exploring its potential benefits for allergic conditions, autoimmune disorders, and inflammatory diseases.

The role of L. reuteri in metabolic health has received increased attention, with studies investigating its effects on insulin sensitivity, fat metabolism, and obesity-related inflammation. The potential of L. reuteri as an adjunct therapy for Helicobacter pylori infection has been further supported by clinical trials, showing improved eradication rates and reduced side effects when used alongside conventional treatment.

Applications in oral health have expanded beyond dental caries and gingivitis to include potential benefits for periodontitis, halitosis, and oral candidiasis. The use of L. reuteri during pregnancy and early life has been studied for potential benefits in preventing allergic diseases, with some promising results for eczema prevention. Recent taxonomic revisions have proposed reclassifying L.

reuteri as Limosilactobacillus reuteri, reflecting updated understanding of bacterial phylogeny, though both names remain in use. Ongoing research is exploring the potential of L. reuteri in new areas such as skin health, urogenital health, and as an adjunct therapy in cancer treatment to reduce side effects and support immune function.

Urbańska M, Szajewska H. The efficacy of Lactobacillus reuteri DSM 17938 in infants and children: a review of the current evidence. Eur J Pediatr. 2014;173(10):1327-1337., Szajewska H, Gyrczuk E, Horvath A. Lactobacillus reuteri DSM 17938 for the management of infantile colic in breastfed infants: a randomized, double-blind, placebo-controlled trial. J Pediatr. 2013;162(2):257-262., Indrio F, Di Mauro A, Riezzo G, et al. Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized clinical trial. JAMA Pediatr. 2014;168(3):228-233., Jones ML, Martoni CJ, Prakash S. Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri NCIMB 30242: a randomized controlled trial. Eur J Clin Nutr. 2012;66(11):1234-1241., Mu Q, Tavella VJ, Luo XM. Role of Lactobacillus reuteri in Human Health and Diseases. Front Microbiol. 2018;9:757.

Lactobacillus reuteri DSM 17938 for Prevention of Necrotizing Enterocolitis in Very Low Birth Weight Infants (ClinicalTrials.gov Identifier: NCT03941782), Efficacy of Lactobacillus reuteri in Children with Functional Abdominal Pain (ClinicalTrials.gov Identifier: NCT04073927), Lactobacillus reuteri NCIMB 30242 for Management of Metabolic Syndrome (ClinicalTrials.gov Identifier: NCT04125563), Effects of Lactobacillus reuteri on Bone Density in Postmenopausal Women (ClinicalTrials.gov Identifier: NCT04153214), Lactobacillus reuteri for Prevention of Antibiotic-Associated Diarrhea in Children (ClinicalTrials.gov Identifier: NCT03902561)

Lactobacillus reuteri has a substantial body of scientific evidence supporting several of its health benefits, with the strongest evidence for specific strains in particular applications. The most robust evidence exists for L. reuteri DSM 17938 in the management of infantile colic, with multiple randomized controlled trials and meta-analyses demonstrating significant reduction in crying time in breastfed infants with colic. This strain has also shown efficacy in preventing and treating acute gastroenteritis and antibiotic-associated diarrhea in children.

For cholesterol management, L. reuteri NCIMB 30242 has demonstrated significant cholesterol-lowering effects in adults with hypercholesterolemia through increased bile salt hydrolase activity and other mechanisms. Multiple clinical trials have shown reductions in LDL cholesterol and total cholesterol with this specific strain. In the area of oral health, several clinical trials have shown benefits of L.

reuteri for reducing gingivitis, plaque formation, and periodontal pocket depth. The strains DSM 17938 and ATCC 55730 have been most commonly studied for oral health applications. For bone health, animal studies with L. reuteri ATCC PTA 6475 have shown promising results in preventing bone loss in models of osteoporosis, primarily through anti-inflammatory mechanisms and modulation of bone metabolism.

Human studies in this area are limited but ongoing. L. reuteri has also shown potential benefits for immune function, with several studies demonstrating reduced incidence of respiratory and gastrointestinal infections in both children and adults. Some studies have also suggested potential benefits for allergic conditions, though the evidence is less consistent in this area.

The quality of evidence varies across different applications, with the strongest evidence coming from multiple well-designed randomized controlled trials for infantile colic (DSM 17938) and cholesterol management (NCIMB 30242). For other applications, the evidence may be limited by smaller sample sizes, heterogeneity in study designs, or inconsistent results across studies. It’s important to note that the effects of L. reuteri are highly strain-specific, with different strains showing efficacy for different conditions.

The DSM 17938, NCIMB 30242, and ATCC PTA 6475 strains have the most extensive research support for their respective applications. Future research directions include larger, longer-term clinical trials, studies on specific mechanisms of action, exploration of strain-specific effects, and investigation of potential applications in metabolic and neurological disorders. Ongoing trials are exploring the potential benefits of L. reuteri for conditions such as necrotizing enterocolitis in premature infants, functional abdominal pain, metabolic syndrome, and bone health in postmenopausal women.